Examining 1:1 Versus 4:1 Packed Red Blood Cell to Fresh Frozen Plasma Ratio Transfusion During Pediatric Burn Excision
Journal of burn care & research : official publication of the American Burn Association. 2020
Blood transfusions following major burn injury are common due to operative losses, blood sampling, and burn physiology. While massive transfusion improves outcomes in adult trauma patients, literature examining its effect in critically ill children is limited. The study purpose was to prospectively compare outcomes of major pediatric burns receiving a 1:1 vs 4:1 packed red blood cell (PRBC) to fresh frozen plasma (FFP) transfusion strategy during massive burn excision. Children with >20% total body surface area (TBSA) burns were randomized to a 1:1 or 4:1 PRBC/FFP transfusion ratio during burn excision. Parameters examined include patient demographics, burn size, Pediatric Risk of Mortality (PRISM) scores, Pediatric Logistic Organ Dysfunction (PELOD) scores, laboratory values, total blood products transfused, and the presence of blood stream infections or pneumonia. A total of 68 children who met inclusion criteria were randomized into two groups (n=34). Mean age, PRISM scores, estimated blood loss (600 mL (400 - 1175 mL) v 600 mL (300 - 1150 mL), p = 0.68), ventilator days (5 v 9, p = 0.47), and length of stay (57 v 60 days, p = 0.24) had no difference. No differences in frequency of blood stream infection (20 v 18, p = 0.46) or pneumonia events (68 v 116, p = 0.08) were noted. On multivariate analysis, only TBSA burn size, inhalation injury, and PRISM scores (p < 0.05) were significantly associated with infections.
Transfusion Requirement in Burn Care Evaluation (TRIBE): a multicenter randomized prospective trial of blood transfusion in major burn injury
Annals of Surgery. 2017;266((4):):595-602
OBJECTIVE Our objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality. BACKGROUND Patients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown. METHODS This prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7-8 g/dL) or liberal (hemoglobin 10-11 g/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. RESULTS Eighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusions: mean 20.3 +/- 32.7 units, median = 8 (interquartile range: 3, 24) versus mean 31.8 +/- 44.3 units, median = 16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, chi test). CONCLUSIONS A restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).
Randomized comparison of packed red blood cell-to-fresh frozen plasma transfusion ratio of 4: 1 vs 1: 1 during acute massive burn excision
Journal of Burn Care & Research.. 2016;38((3):):194-201
This prospective randomized controlled trial compared 1:1 vs 4:1 packed red blood cell with fresh frozen plasma (PRBC/FFP) transfusion strategy on outcomes in children with >20% TBSA burns. Children with >20% TBSA burns were randomized to a 1:1 or 4:1 PRBC/FFP transfusion ratio during burn excision. Parameters measured included demographics, TBSA burn, and Pediatric Risk of Mortality scores. Laboratory values recorded preoperatively, 1 hour, 12 hours, 24 hours, and 1 week postoperatively included prothrombin time, partial thromboplastin time (PTT), international normalized ratio, fibrinogen, protein C, and antithrombin C (AIII). Total number of blood products transfused intraoperatively and during hospitalization was recorded. Forty-five children were enrolled, 22 in the 1:1 and 23 in the 4:1 group. Groups were similar in age, TBSA, and Pediatric Risk of Mortality score. Preoperative fibrinogen, AIII, protein C, hemoglobin, PTT, international normalized ratio, and platelets were similar. In the first two excisions, the 1:1 group received significantly more FFP per patient. Volume of PRBC and overall product transfused did not differ between groups. At 1 hour postoperatively, prothrombin time and PTT were lower and protein C and AIII were higher in the 1:1 group. The 4:1 group was more significantly acidotic 1 hour postexcision. A 1:1 PRBC/FFP transfusion strategy, compared with a 4:1 strategy, decreased postoperative markers of coagulopathy and acidosis immediately after surgery. The strategy did not change the total volume of blood product transfused. This interim analysis was not powered to detect differences in wound healing and length of stay. ES 1559-0488 IL 1559-047X
Albumin in burn shock resuscitation: a meta-analysis of controlled clinical studies
Journal of Burn Care Research. 2016;37((3):):e268-78
Critical appraisal of outcomes after burn shock resuscitation with albumin has previously been restricted to small relatively old randomized trials, some with high risk of bias. Extensive recent data from nonrandomized studies assessing the use of albumin can potentially reduce bias and add precision. The objective of this meta-analysis was to determine the effect of burn shock resuscitation with albumin on mortality and morbidity in adult patients. Randomized and nonrandomized controlled clinical studies evaluating mortality and morbidity in adult patients receiving albumin for burn shock resuscitation were identified by multiple methods, including computer database searches and examination of journal contents and reference lists. Extracted data were quantitatively combined by random-effects meta-analysis. Four randomized and four nonrandomized studies with 688 total adult patients were included. Treatment effects did not differ significantly between the included randomized and nonrandomized studies. Albumin infusion during the first 24 hours showed no significant overall effect on mortality. However, significant statistical heterogeneity was present, which could be abolished by excluding two studies at high risk of bias. After those exclusions, albumin infusion was associated with reduced mortality. The pooled odds ratio was 0.34 with a 95% confidence interval of 0.19 to 0.58 (P < .001). Albumin administration was also accompanied by decreased occurrence of compartment syndrome (pooled odds ratio, 0.19; 95% confidence interval, 0.07–0.50; P < .001). This meta-analysis suggests that albumin can improve outcomes of burn shock resuscitation. However, the scope and quality of current evidence are limited, and additional trials are needed.
Prospective comparison of packed red blood cell-to-fresh frozen plasma transfusion ratio of 4: 1 versus 1: 1 during acute massive burn excision
The Journal of Trauma and Acute Care Surgery. 2013;74((1):):76-83.
BACKGROUND Acute burn excision results in at least 2% blood volume loss per percent excised; hence, massive blood loss (>50% total blood volume) occurs during major burn excisions. The purpose of this pilot study was to assess safety and prospectively compare the impact of a 4:1 versus a 1:1 packed red blood cell-fresh frozen plasma (PRBC/FFP) transfusion strategy on outcomes in children with burns greater than 20% total body surface area (TBSA). METHODS Children with greater than 20% TBSA burn were randomized to a 1:1 or 4:1 PRBC/FFP ratio during burn excision. Parameters measured on admission included demographics, burn size, and Pediatric Risk of Mortality scores. Laboratory values that were measured preoperatively, 1 hour, 12 hours, 24 hours, and 1 week included prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), fibrinogen, protein C, and antithrombin C (AIII). Total number of blood products transfused during operative interventions and during hospitalization were recorded. RESULTS Groups were similar in age, weight, TBSA, and Pediatric Risk of Mortality scores at admission. Preoperative fibrinogen, antithrombins III (AIII), protein C, hemoglobin, PT/PTT, INR, and platelets were similar between groups. The 1:1 group received more FFP (43.8 +/- 0.03 U in 1:1 group vs. 15.7 +/- 0.07 in the 4:1 group) and less PRBC (40.7 +/- 0.02 U in 1:1 group vs. 73.1 +/- 0.02 U in 4:1 group) than the 4:1 group. Approximately 50% blood volume was replaced with PRBC intraopaeratively. There was no difference in PT/PTT, INR, hemoglobin, or platelets between groups. Protein C and AIII were higher in the 1:1 group. Cost of FFP and PRBC were lower in the 1:1 group. CONCLUSION A 1:1 PRBC/FFP transfusion strategy increased FFP use, decreased overall PRBC use, and resulted in higher AIII and protein C postoperatively without a difference in INR or PT/PTT. This may represent compensatory changes in the 4:1 group in response to intraoperative blood loss. LEVEL OF EVIDENCE Therapeutic, level II.
Comparison of fibrin sealant and staples for attaching split-thickness autologous sheet grafts in patients with deep partial- or full-thickness burn wounds: a phase 1/2 clinical study
Journal of Burn Care & Research : Official Publication of the American Burn Association. 2007;28((3):):401-8.
We undertook a multicenter, randomized, controlled, phase 1/2 clinical study to investigate the safety and efficacy of a fibrin sealant containing 4 IU/ml thrombin (FS 4IU) for the attachment of autologous sheet grafts in patients with deep partial-thickness or full-thickness burn wounds. Fibrin sealant (FS 4IU) was compared with staples for adherence of sheet grafts in 40 patients. Patients had to have burn wounds measuring 40% TBSA or less with two comparable test sites measuring between 1% and 4% TBSA each. Wound beds were prepared before treatment assignment, which was randomized. Percent area of hematoma/seroma at Day 1 (P = . 0138) and questionable viability at Day 5 (P = . 0182) were significantly less for FS 4IU-treated sites. Median percent area of graft survival on Day 14 was 100% for both treatments (P = . 3525). The percentage of completely closed sites generally was greater for FS 4IU-sites on Days 5 to 91; the maximum difference occurred at Day 28 (79. 5% vs 59%; P = . 0215). The safety profile of FS 4IU was excellent as indicated by the lack of any related serious adverse experiences. These findings indicate that FS 4IU is safe and effective for fixation of skin grafts, with outcomes similar to or better than staple fixation. The data suggest that FS 4IU is a promising candidate for further clinical studies focusing on skin graft adhesion and burn wound healing.
A multicenter clinical trial to evaluate the topical hemostatic efficacy of fibrin sealant in burn patients
Journal of Burn Care & Rehabilitation. 2001;22((2):):99-103.
Current surgical management of deep partial-thickness and full-thickness burn wounds involves early excision and grafting. Blood loss during these procedures can be profound, thus prompting the use of topical hemostatic agents to control and minimize hemorrhage during grafting. The primary endpoint of this multicenter trial was to evaluate the efficacy of fibrin sealant as a topical hemostatic agent during skin grafting. The secondary endpoint was to obtain data to support the existing safety profile of a human fibrin sealant (FS) in participating patients as indicated by the type, severity, and frequency of any adverse events within the 24-hour postoperative period. A multicenter prospective, open label, Phase III multicenter, randomized, comparative clinical trial evaluated the use of fibrin sealant in burn patients undergoing skin graft procedures. Each patient served as his or her own control in this randomized, unblinded study of the effect on time to hemostasis in donor sites treated with the investigational FS product. At operation, 1 contiguous donor skin harvest site was bisected into 2 equal halves, 1 of which was then randomly selected and treated with fibrin sealant. At the end of the fibrin sealant application, the time to hemostasis in each of the donor site halves was identified by the operating surgeon and recorded by the research coordinator. The use of any other topical hemostatic agents was prohibited. A significant difference (P < .001) was demonstrated in the mean time to hemostasis between the fibrin sealant treated donor sites when compared painwise to the control sites. The significant difference was consistent across the 6 participating study centers. There were no adverse events associated with the use of fibrin sealant. The investigational FS product was shown to be efficacious, because it significantly decreases the time to hemostasis at the donor skin harvest site in patients undergoing skin grafting and was noted not to cause any adverse reactions.
Multicenter trial to evaluate the safety and potential efficacy of pooled human fibrin sealant for the treatment of burn wounds
Journal of Trauma-Injury Infection & Critical Care. 1999;46((3):):433-40.
OBJECTIVE The primary purpose of this multicenter study was to evaluate the safety and potential efficacy of a solvent/detergent-treated commercial fibrin sealant (human) for topical hemostasis in skin grafting. METHODS The study involved a prospective evaluation of changes in viral titers in patients with burns less than 15% after treatment with fibrin sealant (human). Each patient served as his/her own control for an unblinded, randomized comparison of donor site hemostasis and healing. Preoperative serum was obtained to screen for viral titers. At autografting, the recipient site and one of two randomly chosen donor sites were treated with fibrin sealant (human). The use of other hemostatic agents, including epinephrine was prohibited. Each donor site was covered with gauze to collect blood for estimation of the relative amount of bleeding. The healing of the graft and donor sites was observed. Viral titers and wounds were checked monthly for 6 months, and at 9 and 12 months postoperatively. RESULTS Viral titers for human immunodeficiency virus; hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus were obtained before and after treatment. Of 47 patients, 34 completed the full year of observation. After treatment, there were no seroconversions to any of the aforementioned viruses. Bleeding at the recipient site appeared well controlled with fibrin sealant (human). Although investigators felt that fibrin sealant (human) improved donor site hemostasis, differences in hemoglobin measurements of blood-soaked dressings failed to reach significance. No differences were noted with regard to acceleration of donor site healing, graft take, or scar maturation at the two groups of donor sites. Anecdotally, the maturation of the recipient site appeared to be accelerated. CONCLUSION Fibrin sealant (human) is safe for use during excision and grafting, and its topical hemostatic potential needs to be examined in patients with larger burns. Its role in scar maturation also needs to be investigated.
Maintenance of serum albumin levels in pediatric burn patients: a prospective, randomized trial
Journal of Trauma-Injury Infection & Critical Care. 1995;39((1):):67-73; discussion 73-4.
A prospective, randomized trial was performed to determine whether maintaining serum albumin levels in burned pediatric patients had any effect on morbidity and mortality. Patients < 19 years of age with burns > 20% total body surface area were randomized to receive supplemental albumin to maintain levels 2.5 to 3.5 g/dL ("High Albumin") or were given albumin only if levels dropped < 1.5 g/dL ("Low Albumin") after completing burn shock resuscitation. The 36 patients in the Low Albumin group were well matched for age, burn size, depth of injury, and inhalation injury when compared with the High Albumin group (34 patients). As expected, serum albumin levels were significantly lower in the Low Albumin group when compared with the High Albumin group. No differences between groups were noted for resuscitation needs, maintenance fluid requirements, urine output, tube feedings received, days of antibiotic treatment, or ventilatory requirements. No differences in hematology, electrolytes, or nutritional laboratories were found. Finally, length of stay, complication rate, and mortality were not affected by albumin treatment. Albumin supplementation to maintain normal serum levels does not seem to be warranted in previously healthy children who suffer severe burns and who receive adequate nutrition.